© British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.Oligophrenin-1 (Ophn1) encodes a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID) in humans. Loss of function of Ophn1 leads to impairments in the maturation and function of excitatory and inhibitory synapses, causing deficits in synaptic structure, function and plasticity. Epilepsy is a frequent co-morbidity in patients with Ophn1-dependent XLID, but the cellular bases of hyperexcitability are poorly understood. Here we report that male mice knock-out (KO) for Ophn1 display hippocampal epileptiform alterations, which are associated with changes in parvalbumin-, somatostatin- and neuropeptide Y-positive interneurons. https://www.selleckchem.com/products/acetosyringone.html Since loss of function of Ophn1 is related to enhanced activity of Rho-associated protein kinase (ROCK) and protein kinase A (PKA), we attempted to rescue Ophn1-dependent pathological phenotypes by treatment with the ROCK/PKA inhibitor Fasudil. While acute administration of Fasudil had no impact on seizure activity, seven weeks of treatment in adulthood were able to correct electrographic, neuroanatomical and synaptic alterations of Ophn1 deficient mice. These data demonstrate that hyperexcitability and the associated changes in GABAergic markers can be rescued at the adult stage in Ophn1-dependent XLID through ROCK/PKA inhibition.Significance Statement In this study we demonstrate enhanced seizure propensity and impairments in hippocampal GABAergic circuitry in Ophn1 mouse model of XLID. Importantly, the enhanced susceptibility to seizures, accompanied by an alteration of GABAergic markers were rescued by ROCK/PKA inhibitor Fasudil, a drug already tested on humans. Since seizures can significantly impact the quality of life of XLID patients, the present data suggest a potential therapeutic pathway to correct alterations in GABAergic networks and dampen pathological hyperexcitability in adults with XLID. Copyright © 2020 the authors.We can adapt flexibly to environment changes and search for the most appropriate rule to a context. The orbital prefrontal cortex (PFo) has been associated with decision making, rule generation and maintenance, and more generally has been considered important for behavioral flexibility. To better understand the neural mechanisms underlying the flexible behavior, we studied the ability to generate a switching signal in monkey PFo when a strategy is changed. In the strategy task, we used a visual cue to instruct two male rhesus monkeys either to repeat their most recent choice (i.e. stay strategy) or to change it (i.e. shift strategy). To identify the strategy switching-related signal, we compared non-switch and switch trials, which cued the same or a different strategy from the previous trial, respectively. We found that the switching-related signal emerged during the cue presentation and it was combined with the strategy signal in a subpopulation of cells. Moreover, the error analysis showed that the activityectively using a stay or a shift strategy. We found that PFo neurons were modulated by the strategy switching signal, pointing to the importance of PFo in behavioral flexibility by generating control over the switching of strategies. Copyright © 2020 the authors.Regulated secretion is controlled by Ca2+-sensors with different affinities and subcellular distributions. Inactivation of Syt1, the main Ca2+-sensor for synchronous neurotransmission in many neurons, enhances asynchronous and spontaneous release rates, suggesting that Syt1 inhibits other sensors with higher Ca2+ affinities and/or lower cooperativities. Such sensors could include Doc2a and -b, which have been implicated in spontaneous and asynchronous neurotransmitter release, and compete with Syt1 for binding SNARE complexes. Here we tested this hypothesis using triple-knockout mice. Inactivation of Doc2a and Doc2b in Syt1-deficient neurons did not reduce the high spontaneous release rate. Overexpression of Doc2b variants in triple-knockout neurons reduced spontaneous release but did not rescue synchronous release. A chimeric construct in which the C2AB domain of Syt1 was substituted by that of Doc2b did not support synchronous release either. Conversely, the soluble C2AB domain of Syt1 did not affect spontaby reintroducing wild type and mutant proteins in triple-knockout neurons, and conclude that the sensors are highly specialized for different phases of release. Copyright © 2020 the authors.INTRODUCTION OSPREY personal armour has been issued to UK forces since 2005. From 2015, the VIRTUS personal armour and load carriage system have been progressively replacing OSPREY. In 2016, the ban on women in ground close combat roles throughout the UK's Armed Forces was lifted. In anticipation of this, work has been ongoing to prepare future ballistic protection programmes for a potential increase in the number of female users. METHOD A human factors questionnaire was provided to 150 female users of OSPREY body armour to complete while on combat operations in Afghanistan. The questionnaire asked the users to rate the comfort of their OSPREY body armour along with their ability to carry out basic tasks. Other background data such as size of body armour worn and bra size were also collected for the analysis. RESULTS The female participants reported various types of discomfort when wearing their OSPREY body armour, with 135 instances of discomfort experienced in the hip region, for example. Challenges were reported in the ability to carry out basic movements, with the tasks rated on a Likert scale as difficult or very difficult by between 29% and 59% of participants. In addition, a restriction in ability to access personal equipment worn on the person (including pouches, trouser pockets) was commented on by 39% of participants. CONCLUSIONS Female users reported challenges relating to the fit and function of OSPREY body armour. The VIRTUS body armour system for UK Armed Forces Personnel has already addressed many of the reported issues with OSPREY. Further optimisation for VIRTUS with regard to female users is planned and includes sizing of ballistic hard plates. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.